Ketamine for Rescue Sedation in Severe Behavioral Disturbance

Background

Sedation of the agitated and aggressive patient is a frequently encountered problem in the Emergency Department (ED).Whether the etiology of the agitation is intoxication, psychiatric, or organic, these patients require quick and efficient chemical sedation because they are both a danger to themselves and others in the ED.The majority of these patients are successfully sedated with antipsychotics or benzodiazepines (Downes 2009).

A small number of these patients however, remain difficult to sedate despite multiple doses of medication (Calver 2012).One study showed only 8% of patients were not sedated after 1 or 2 doses of droperidol, and only 3% after 3 doses (Calver 2015). Although uncommon, these difficult –to-sedate patients consume considerable resources and time in the ED. Additionally, they pose continued threats to themselves as well as ED staff and other patients.

Escalating doses of benzodiazepines are a frequent first choice for difficult-to-sedate patients. However, there is some evidence that benzodiazepines alone and combinations of benzodiazepines and antipsychotics are associated with higher rates of adverse effects than antipsychotics alone (Isbister 2010, Calver 2015).Additionally, there exists a significant subset of patients who’s agitation is refractory to benzodiazepines due to abuse and cross tolerance. Ketamine may be a safer alternative.

There is limited data available on the sedation of acutely agitated patients in the ED that have been resistant to standard medications. Ketamine has been successfully used to sedate severely agitated out-of-hospital patients (Scheppke 2014, Le Cong 2012). Hopper 2015 found that ketamine could be used as an initial drug for sedation in the ED but that providers often required other medications afterwards.In this study however, the median dose of ketamine given was 200mg intramuscularly (IM).

Clinical Question

Is ketamine a safe and effective rescue option for sedation in the acutely agitated patient in the ED?

Population

Patients > 16 years old with acute behavioral disturbance recruited as part of the DORM II study that required physical restraint and parenteral sedation (had a score of 2 to 3 on the Sedation Assessment Tool) *see Appendix
Patients who remained agitated and aggressive after initial sedation and received ketamine as additional sedation

Intervention

4-6 mg/kg of intramuscular ketamine administered as a third-line agent in patients being managed with a standardized sedation protocol (initial 10mg dose of intramuscular droperidol, second dose of 10mg droperidol if patient not sedated within 15 minutes)

Outcomes

Primary: The number of patients who failed to achieve sedation within 120 minutes of ketamine administrationSecondary:
Time to sedation from the initial onset of acute behavioral disturbance
Time to sedation after administration of ketamine
Any adverse effects (airway obstruction, oxygen saturation less than 90%, respiratory rate < 12 breaths/min, systolic blood pressure (SBP) less than 90 mmHg)
Change in pulse rate and blood pressure after ketamine administration

Limitations

Observational trial. Ketamine was not compared to an alternative agent

The primary outcome of sedation at 120 minutes is a suboptimal one. Optimally, we would like the patient sedated rapidly (< 10-20 minutes)

Small sample size of patients receiving ketamine

Not all patients received the same amount or type of sedation medication(s) prior to the use of ketamine as a rescue drug

Droperidol is not commonly used in the US for sedation of the agitated patient limiting applicability of these results to US patients

There was variability in the timing between droperidol doses and ketamine administration so it is not possible to determine whether the ultimate sedation of the patient was solely due to the ketamine or a delayed response of initial medication

Study was a subgroup analysis from a study that was designed initially to assess droperidol

Author's Conclusions

“Ketamine appeared effective and did not cause obvious harm in this small sample and is a potential option for patients who have failed previous attempts at sedation. A dose of 4 to 6 mg/kg is suggested, and doses less than 200 mg are associated with treatment failure.”

Our Conclusions

Ketamine appears to be an effective rescue sedation option for the difficult-to-sedate, acutely agitated patient in the ED. In this study only 10% of acutely agitated patients in the ED failed sedation with ketamine at 120 minutes. In addition, the majority of the patients that were not successfully sedated were likely under dosed (less than 4-6 mg /kg) per the study’s sedation protocol.
Side effects were low in this study but conclusions on safety cannot be made with this small of a study population. However, there are multiple other studies as well as significant clinical experience using ketamine for sedation without significant safety issues.

Potential Impact To Current Practice

IM ketamine is already frequently used in many EDs (particularly outside the US) for sedation of the acutely agitated patient. The data here is limited by a number of factors and doesn’t necessarily change practice.

Bottom Line

IM ketamine may be considered an effective agent for sedation of the difficult -to-sedate, acutely agitated patient in the ED when dosed appropriately (4-6 mg/kg).